Short-term Blinatumomab Intensification for MRD-Negative Acute B-Cell Lymphoblastic Leukemia Before Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective, Multicenter, Randomized Controlled Study
This is a prospective, multicenter, randomized controlled trial designed to evaluate whether short-term blinatumomab intensification before allogeneic hematopoietic stem cell transplantation (allo-HSCT) can improve survival outcomes in adults with high-risk BCR::ABL1-negative B-cell acute lymphoblastic leukemia (B-ALL) who have achieved measurable residual disease (MRD) negativity. Blinatumomab, a CD19/CD3 bispecific T-cell engager, has shown promising efficacy in eradicating MRD and prolonging survival in B-ALL patients. In this study, eligible participants will be randomly assigned to receive either short-term blinatumomab consolidation prior to allo-HSCT or proceed directly to allo-HSCT. The primary endpoint is relapse-free survival (RFS). This study aims to optimize treatment strategies and improve long-term outcomes for patients with high-risk BCR::ABL1-negative B-ALL.
• 1\. Diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) according to the 2022 WHO classification.
• 2\. Age between 18 and 65 years. 3. Meets the National Comprehensive Cancer Network (NCCN) criteria for high-risk B-ALL, based on clinical or cytogenetic/molecular features:
• Clinical high-risk features (any of the following):
‣ Age \> 35 years
⁃ Peripheral WBC count \> 30 × 10⁹/L
⁃ Cytogenetic/molecular high-risk features (any of the following):
• Cytogenetic and molecular high-risk features (at least one of the following):
‣ Hypodiploidy (\<44 chromosomes)
⁃ TP53 mutation
⁃ KMT2A rearrangement
⁃ MLL rearrangement
⁃ HLF rearrangement
⁃ ZNF384 rearrangement
⁃ MEF2D rearrangement
⁃ MYC rearrangement
⁃ BCR-ABL1-like (Ph-like) ALL, including:
‣ JAK pathway rearrangements (CRLF2r, EPORr, JAK1/2/3r, TYK2r, SH2B3 mutation, IL7R mutation, JAK1/2/3 mutations)
‣ ABL-class rearrangements (ABL1, ABL2, PDGFRA, PDGFRB, FGFR1)
‣ Other kinase fusions (e.g., NTRK3r, FLT3r, LYNr, PTK2Br)
‣ PAX5alt
‣ t(9;22)(q34.1;q11.2); BCR-ABL1 with IKZF1 mutation and/or prior chronic myeloid leukemia (CML)
‣ Intrachromosomal amplification of chromosome 21 (iAMP21)
‣ IKZF1 alteration
‣ Complex karyotype (≥5 chromosomal abnormalities) 4. CD19-positive by immunophenotyping. 5. BCR::ABL1-negative. 6. Achieved complete remission (CR) after induction therapy. 7. Measurable residual disease (MRD)-negative by flow cytometry (FCM). 8. Availability of a matched sibling donor, haploidentical related donor, or matched/unmatched unrelated donor.
∙ 9\. ECOG performance status score of 0-2. 10. Creatinine clearance ≥ 60 mL/min (by Cockcroft-Gault formula). 11. AST and ALT ≤ 3 × upper limit of normal (ULN); total bilirubin ≤ 2 × ULN. 12. Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiography. 13. Expected survival \> 8 weeks. 14. Signed written informed consent, with ability to understand and comply with the study protocol.